Current Projects
National Institutes of Health RO1 DK061568
Cysteine, Intestinal Thiols, and Goblet Cell Development
HR Gaskins (PI); Co-investigator: Sharon Donovan
Tests the hypothesis that the lack of luminal cysteine is a primary insult perceived by the parenterally nourished intestinal epithelium, and that the functional endpoint of this nutritional deficiency is a more oxidized intracellular redox potential, leading to goblet cell expansion. Thus, we propose that mucus-producing goblet cells are guardians of mucosal redox homeostasis.
National Institutes of Health RO1 CA135379
Diet and Gastrointestinal Cancer Risk in African Americans and Rural Africans
PI: SJ O’Keefe, M.D., University of Pittsburgh School of Medicine
PI UIUC subcontract: HR Gaskins
Tests the hypothesis that the risk of developing cancer of the colon is determined by the interaction between diet and resident microbiota, which influences the level of chronic inflammation and epithelial proliferation - and therefore cancer risk – in the colonic mucosa. Study will examine 20 healthy middle aged subjects from the population of African Americans in the Pittsburgh area and compare them to the same number of native Africans (in South Africa) before and after dietary switch in both groups between a high resistant starch, low meat diet (African diet) to a high red meat, low carbohydrate "westernized" diet.
National Institutes of Health R21 EB004513
Engineered Platforms to Control Intracellular Redox
Paul Kenis (Co-PI) Chemical & Biomolecular Engineering; Co-PI: HR Gaskins
This project focuses on the design and validation of: 1) Engineered electrochemical platforms for cell studies that permit precise control of the intracellular redox environment; and 2) FRET-based redox biosensors that permit visual monitoring of intracellular and intraorganellar redox potentials.
National Institutes of Health RO3 A1070245A
Optimizations of rRNA-based microbial analyses
GJ Olsen (PI) Microbiology and Institute for Genomic Biology
Co-Investigators: HR Gaskins, BA Wilson
The goal of the project is to improve analyses of microbial communities by their rRNA gene content.
Carle UIUC Translational Research Program
Genetic Variation in Mucosal Defense and Inflammatory Bowel Disease
HR Gaskins (PI); Co-Investigators: Eugene Greenberg, Carle Foundation Hosptial; Steve Blanke, Rod Mackie, Richard Tapping, Sheng Zhong
A clinical study in which patients presenting with Crohn’s disease or ulcerative colitis will be compared with appropriately matched controls to determine the extent to which defined clinical features of IBD are associated with: 1) specific acidomucin chemotype patterns; or 2) individual signatures of hydrogenotrophic microbes associated with ileal or colonic mucosa.
Department of Defense
Small Intestinal Microbial Community in Gulf War Illness
PI: HC Lin, M.D., Univ. New Mexico School of Medicine
PI UIUC subcontract: Rex Gaskins
Clinical study focused on hypothesis that Gulf War Illness (GWI) is driven by small intestinal bowel overgrowth and that the small intestine of patients with GWI have more and/or different bacteria than controls. The work at UIUC will use molecular approaches to specifically examine the hypothesis that sulfate reducing bacteria dominate the small intestinal microbiota in GWI patients and to determine the extent to which it is possible to reduce their density with antibiotic therapy.
Bristol-Myers Squibb Freedom to Discover Nutrition Research Grant
Defining the Nutritional Requirements of the Developing Intestinal Ecosystem
SM Donovan (PI); Co-Investigators: George Fahey, Peter Garlick, HR Gaskins, Rod Mackie, Larry Schook, Kelly Swanson, Kelly Tappenden, Bryan White
This project focuses on the use of the neonatal pig as a model to study the influence of the intestinal microbiota on the nutritional status of newborns (premature births).
Recent Publications
Conour JE, Graham WV, Gaskins HR (2004) A combined in vitro/bioinformatic investigation of redox regulatory mechanisms governing cell cycle progression. Physiol Genomics 18(2):196-205.
Attene-Ramos MS, Kitiphongspattana K, Ishii-Schrade KB, Gaskins HR (2005) Temporal changes of multiple redox couples from proliferation to growth arrest in IEC-6 intestinal epithelial cells. Am J Physiol Cell Physiol 289(5):C1220-1228.
Attene-Ramos MS, Wagner ED, Plewa MJ, Gaskins HR (2006) Evidence that hydrogen sulfide is a genotoxic agent. Mol Cancer Res 4(1):9-14.
Attene-Ramos MS, Wagner ED, Gaskins HR, Plewa MJ (2007) Hydrogen sulfide induces direct radical associated DNA damage. Mol Cancer Res 5(5):455-9.
Chowdhury SR, King DE, Willing BP, Band MR, Beever JE, Lane AB, Loor JJ, Marini JC, Rund LA, Schook LB, Van Kessel AG, Gaskins HR (2007) Transcriptome profiling of the small intestinal epithelium in germfree versus conventional piglets. BMC Genomics 8(1):215.
Kolossov VL, Spring B, Sokolowski A, Conour JE, Clegg RM, Kenis PJA, Gaskins HR (2008) Engineering redox-sensitive linkers for genetically encoded FRET-based biosensors. Exp Biol Med 233(2): 238-48.
Gaskins, HR, Croix JA, Nakamura N, Nava GM (2008) Impact of the intestinal microbiota on the development of mucosal defense. Clin Infect Dis 46(Suppl 2): S80-86.
Nava GM, Lee DY, Ospina JH, Cai SY, Gaskins HR. (2009) Genomic analyses reveal a conserved glutathione homeostasis pathway in the invertebrate chordate Ciona intestinalis. Physiol Genomics (in press).
Recent Meetings and Abstracts
Experimental Biology 2009
April 18-22, New Orleans, LA.
Diet and intestinal sulfate reducing bacteria populations distinguish native Africans from Caucasian and African Americans.
GM Nava, J Ou, SJ O'Keefe, HR GaskinsInterleukin (IL)-13 modulation of goblet cell function is dependent on state of differentiation.
JA Croix, CT Collier, TA Khan, HR Gaskins
Digestive Disease Week
May 30 - June 4, 2009, Chicago, IL
Cysteine dioxygenase expression is restricted to the secretory lineage in the small intestine and colon.
JA Croix, I Ueki, MH Stipanuk, E Greenberg, HR GaskinsDiversity of colonic Archaea and sulfate reducing bacteria populations in native Africans differs from those in Caucasian and African Americans.
GM Nava, J Ou, SJD O'Keefe, HR Gaskins
